Fig. 36.9 ). Increased flow bends the primary cilium in principal cells, which activates the PKD1/PKD2 Ca++-conducting channel complex. This allows more Ca++ to enter principal cells and increases intracellular [Ca++]. The increase in [Ca++] activates BK K+ channels in the apical plasma membrane, which enhances K+ secretion from the cell into the tubule fluid. Increased flow may also stimulate secretion of K+ by other mechanisms. As flow increases, such as after administration of diuretics or as the result of an increase in ECFV, so does the [Na+] of tubule fluid. This increase in [Na+] facilitates entry of Na+ across the apical membrane of ASDN cells, thereby decreasing the cells’
K+ K+ ° Flow stimulates Na+ entry, which reduces Vm ° Flow Cilia bend activates PKD1/PKD2 and Ca++ entry ° Flow bends cilia ° Ca++ activates Na+ Ca++ ATP 1 25 4 3 • Fig. 36.9 Cellular mechanism whereby an increased flow rate of tubule fluid stimulates secretion of K+ by principal cells. See text for details.
interior negative membrane potential. This depolarization of the cell membrane potential increases the electrochemical driving force that promotes secretion of K+ across the apical cell membrane into tubule fluid. In addition, increased uptake of Na+ into cells activates the Na+,K+-ATPase in the basolateral membrane, thereby increasing uptake of K+ across the basolateral membrane and consequently elevating [K+]. However, it is important to note that an increase in flow rate during a water diuresis does not have a significant effect on excretion of K+ , most likely because during a water diuresis the [Na+] of tubule fluid does not increase as flow rises.
Another factor that modulates secretion of K+ is the [H+] of ECF. Acute alterations (within minutes to hours) in the pH of plasma influences secretion of K+ by the ASDN. Alkalosis (i.e., plasma pH above normal) increases secretion of K+ , whereas acidosis (i.e., plasma pH below normal) decreases it. An acute acidosis reduces K+ secretion via two mechanisms: (1) it inhibits Na+,K+-ATPase and thereby reduces cell [K+] and the electrochemical driving force for exit of K+ across the apical membrane, and (2) it reduces the permeability of the apical membrane to K+ . Alkalosis has the opposite effects.
The effect of metabolic acidosis on excretion of K+ is time dependent. As already noted, and illustrated in
Fig. 36.10 , acute metabolic acidosis reduces K+ excretion. However, when metabolic acidosis lasts for several days, urinary K+ excretion is stimulated (see
Fig. 36.10 ). This occurs because chronic metabolic acidosis decreases reabsorption of water and solutes (e.g., NaCl) by the proximal tubule by
ROMK is the primary channel in the apical membrane of principal cells that mediates K+ secretion. Four ROMK subunits make up a single channel. In addition the BK K+ channel, which is activated by elevations in intracellular [Ca++], is also expressed in the apical membrane. The BK channel mediates the flow-dependent increase in K+ secretion discussed earlier. Interestingly, knockout of the KCNJ1 gene (ROMK) causes increased excretion of NaCl and K+ by the kidneys, thereby leading to reduced ECFV and hypokalemia. Although this effect is somewhat perplexing, it should be noted that ROMK is also expressed in the apical membrane of the thick ascending limb (TAL) of Henle’s loop, where it plays a very important role in recycling of K+ across the apical membrane, an effect that is critical for operation of the Na+/ K+/2Cl− symporter (see